Epilepsy drugs Flashcards
1
Q
Benzos
A
IV:
- Diazepam
- Midazalam
- Lorazepam
Non hepatic metabolism:
- Lorazepam
- Oxazepam
- Temazepam
MOA:
- Bind at interface of alpha and gamma subunit of GABAa complex
- Allosterically potentiate the effect of GABA, increasing the frequency of opening of the Cl channel
- Working through Bz1 receptor, causes sedation
- Working through Bz2 receptor, anxiolytic and impairment of cognitive functions
SE:
- Drowsiness, increasing CNS depression
- Hypotension
- Headache
- Anterograde amnesia
- Skin rash
- Nausea
2
Q
carbemazepine
A
MOA:
- blocks axonal voltage dependent Na channels in their inactive state
- > extends inactivated phase and inhibits generation of rapid action potentials
- effect increases with the rate of neuronal firing
Pharmacodynamics
- 70% protein bound
- metabolised by CYP450
- main metabolite has anticonvulsant activity
- interactions with valproate, lamotragine and phenytoin
SE:
- induces CYP450
- common = nausea rash and GI distress
- CNS depression and diplopia (neurotoxic)
- osteomalacia (vitamin D absorption)
- megaloblastic anaemia (folate absorption)
- aplastic anaemia
- SJS
- hyponatraemia (increase ADH, dilutional)
- teratogenic (cleft lip, spina bifida)
Levels and screening
- levels check 3,6,9 weeks
- goal = 4-12mcg/mL
- HLAB-1502 for asians
3
Q
valproate
A
MOA:
- blocks axonal Na channels
- block T type calcium channels
- inhibits GABA-tranaminase
SE:
- hepatoxicity
- acute pancreatitis
- thombocytopaenia
- alopecia
- teratogenic (spina bifida)
4
Q
lamotragine
A
MOA:
- inactivates voltage dependent sodium channels
- prevents repetitive firing of neurons
SE:
- SJS
- benign rash more common
- nausea
- dizziness
- somnolence
- tremor
- diplopia
- aseptic meningitis
5
Q
Phenytoin
A
MOA
- blocks axonal voltage dependent Na channels in their inactive state
- > extends inactivated phase and inhibits generation of rapid action potentials
- effect increases with the rate of neuronal firing
Pharmacokinetics
- non linear absorption
- zero order kinetics
- induces CYP450
SE
- hursutism
- gingival hyperplasia
- CNS depression
- megaloblastic anaemai
- aplastic anaemia
- osteomalacia
- teratogenic (cleft lip and palate)
6
Q
Avoiding carbemazepine SE’s
A
Baseline blood testing
- WCC
- limited evidence for routine testing
HLAB-1502 in asian (excluding japanese) patients
- SJS with carbamazepine
- maybe phenytoin or lamotrogine
Initial levels
- start low, go slow
- measure levels at 3,6,9 weeks (autoinduction)
- aim for 4-12mcg/mL
Chronic levels
- assess compliance
- attribute symptoms to toxicity
ALWAYS CHECK DRUG INTERACTIONS
Monitor vitamin D
Diary
- seizure events
- triggers
- assess efficacy, compliance
7
Q
Epilepsy pharm management
A
Focal = carbemazepine
Generalised = valproate
First drug trial
-50% response rate
Second
-15% response rate
Adding second drug
- maintain first
- titrate second one up
- trial removal of first
Stopping therapy
- don’t attempt before 2 year seizure free
- 50% chance seizure recurrence
- withdraw slowly 6 weeks - 6 months
- no driving during reduction and for 3 months after last dose
8
Q
seizure in therapeutic range carbemazepine
A
1/3 do not achieve seizure control
- poor compliance
- alcohol
- triggers
- wrong epilepsy syndrome
- wrong drug (50% response to 1st, 15% to 2nd)
- wrong diagnosis (referral to specialist = 50% change diagnosis, 30% psychogenic)
9
Q
epilepsy pharm
A
Patient education
- need for compliance (decreases mortality/hospitalisation)
- avoid sudden withdrawal (status epilepticus)
- avoid known triggers
- seek advice before starting non-prescription meds
- role of sleep deprivation, stress, stimulants and alcohol
- avoid solo swimming, heavy machinary etc
Alcohol
- evidence that 1-2 may not alter seizure activity
- greater than 2 is a known risk
- greatest risk is in withdrawal (no driving post drink)
Driving
- avoid drugs or alcohol
- long drives and sleep deprivation
- increased risk for epilepsy drivers
